Interpretation of the prevention and treatment of COVID-19 in Jiangxi based on "unified coldness and warmness"

Since the outbreak of COVID-19, various regions have introduced their own TCM prevention and treatment methods. However, there are two opposing views on the nature of coldness and warmness. With advanced social development, the thought of the unification of coldness and warmness has developed rapidly, and many doctors gradually have realized the importance and practicability of the unification of coldness and warmness, and began to advocate the unification of coldness and warmness syndrome. The prevention and treatment of COVID-19 in Jiangxi was developed by Professor Wu Bingcai,a master of Chinese medicine, based on the unified idea of cold and temperature, according to the characteristics of humid climate in Jiangxi, and in combination with the characteristics of COVID-19, the anti-toxin prescription for dispelling cold and desiccating dampness and the anti-toxin prescription for clearing heat and dehumidifying, which achieved exact and satisfactory results in clinical application.

Short Sleep Duration as a Risk Factor for Depression, Anxiety and Fatigue in Patients with Leukemia.

Objective: Our study aimed to investigate the level of depression, anxiety, and fatigue in patients with leukemias, and analyze the influence of sleep duration on the mental symptoms of patients with leukemias. Methods: A total of 127 patients were enrolled in our study and completed the questionnaire survey. Self-Assessment Depression Scale (SDS), Self-Assessment Anxiety Scale (SAS), and the Fatigue Scale-14 (FS-14) were adopted. The patient's lifestyle information, including exercise, alcohol abuse, and smoking, was obtained from the patient's self-report. Results: Depression score of patients with sleep duration >8 hours (long duration group) was 56.21±11.63, which was significantly lower than that of patients sleep duration between 6 and 8 hours (medium duration group) with 59.61±8.77 and patients sleep <6 hours (short duration group) with 64.82±6.42 (P = 0.007). Similarly, the anxiety score of long duration group, medium duration group and short duration group was 45.36±11.41, 48.26±6.96 and 53.53±5.87, respectively (P = 0.005). The fatigue score of short duration group is 8.47±2.45, which is higher than others (P = 0.046). To further identify the relationship, we evaluated physical fatigue and mental fatigue levels in patients with or without symptoms of depression. We found that patients with symptoms of depression have a higher score both in physical fatigue and mental fatigue (all p < 0.001). Similar trend was observed in patients with or without symptoms of anxiety (all p < 0.001). However, alzhough patients with leukemia in long duration group have the highest score of physical fatigue (p = 0.016), no significant difference in mental fatigue was found in different sleeping duration group (p = 0.587). Furthermore, multivariate analyses were conducted and revealed that sleep duration was the independent factor associated with depression (OR = 0.270, P = 0.003) and anxiety (OR = 0.473, P = 0.010). Conclusion: For leukemia patients with short sleep duration, a prompt evaluation of their level of depression, anxiety, and fatigue and the initiation of timely interventions is essential.

Trends in Remdesivir Treatment Over the Course of the COVID-19 Pandemic

Background Remdesivir is approved for use in the United States for treatment of COVID-19 requiring hospitalization. Real-world data on trends in remdesivir use may elucidate its benefits and place in therapy. Methods Hospitalized Veterans with a positive SARS-CoV-2 polymerase chain reaction (PCR) test that were treated with remdesivir at a Veterans Affairs Medical Center from May 2020 to April 2021 were included. Monthly trends in remdesivir treatment, as well as patient characteristics and clinical outcomes among patients treated with remdesivir, were assessed with joinpoint regression to calculate average monthly percent change and corresponding 95% confidence intervals (CI). Results A total of 30,333 Veterans were hospitalized with a positive PCR test over the study period, and 13,639 were treated with remdesivir (45%). Throughout the study period, the proportion of Veterans treated with remdesivir increased significantly (4.5% per month, 95% CI 0.5%-8.6%) and median time to remdesivir initiation decreased significantly (12% per month, 95% CI -15.8% to -8.0%). Though demographic characteristics of Veterans treated with remdesivir remained stable, including age, race, and obesity, improvement in clinical outcomes were observed, including median length of hospital stay which decreased by 6.5% per month (95% CI -9.1% to -3.8%), intensive care admissions which decreased by 4.6% per month (95% CI -6.3% to -2.8%) and inpatient mortality which decreased by 6.3% per month (95% CI -9.4% to -3.1%). By April 2021, most patients initiated remdesivir on the day of admission, and the inpatient mortality rate decreased to 7.9% from 19.2% in May 2020. Conclusion Over the course of the COVID-19 pandemic, utilization of remdesivir increased while initiation of remdesivir occurred earlier in the hospital admission, with concurrent reductions in length of hospital stay, intensive care admissions, and inpatient mortality. Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyperactivation (preprint)

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

A comparative survey of betacoronavirus strain molecular dynamics identifies key ACE2 binding sites (preprint)

Comparative functional analysis of the binding interactions between various betacoronavirus strains and their potential human target proteins, such as ACE1, ACE2 and CD26, is critical to our future understanding and combating of COVID-19. Here, employing large replicate sets of GPU accelerated molecular dynamics simulations, we statistically compare atom fluctuations of the known human target proteins in both the presence and absence of different strains of the viral receptor binding domain (RBD) of the S spike glycoprotein. We identify a common interaction site between the N-terminal helices of ACE2 and the viral RBD in all strains (hCoV-OC43, hCoV-HKU1, MERS-CoV, SARS-CoV1, and SARS-CoV-2) and a second more dynamically complex RBD interaction site involving the ACE2 amino acid sites K353, Q325, and a novel motif, AAQPFLL (386-392) in the more recent cross-species spillovers (i.e. absent in hCoV-OC43). We use computational mutagenesis to further confirm the functional relevance of these sites. We propose a "one touch/two touch" model of viral evolution potentially involved in functionally facilitating binding interactions in zoonotic spillovers. We also observe these two touch sites governing RBD binding activity in simulations on hybrid models of the suspected viral progenitor, batCoV-HKU4, interacting with both the human SARS target, ACE2, and the human MERS target, CD26. Lastly, we confirm that the presence of a common hypertension drug (lisinopril) within the target site of SARS-CoV-2 bound models of ACE1 and ACE2 acts to enhance the RBD interactions at the same key sites in our proposed model. In the near future, we recommend that our comparative computational analysis identifying these key viral RBD-ACE2 binding interactions be supplemented with comparative studies of site-directed mutagenesis in order to screen for current and future coronavirus strains at high risk of zoonotic transmission to humans. STATEMENT OF SIGNIFICANCEWe generated structural models of the spike glycoprotein receptor binding domain from recent and past betacoronavirus outbreak strains aligned to the angiotensin 1 converting enzyme 2 protein, the primary target protein of the SARS-CoV-2 virus causing COVID 19. We then statistically compared computer simulated molecular dynamics of viral bound and unbound versions of each model to identify locations where interactions with each viral strain have dampened the atom fluctuations during viral binding. We demonstrate that all known strains of betacoronavirus are strongly interactive with the N-terminal helix region of ACE2. We also identify a more complex viral interaction with three novel sites that associates with more recent and deadly SARS strains, and also a bat progenitor strain HKU4.

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation (preprint)

Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.

Comparative Clinical Characteristics Among Different Age Group of Adult COVID-19 Patients (preprint)

Introduction: Coronavirus disease (COVID-19) is a global infectious disease with a large burden of illness and high healthcare costs.Objectives: This study aimed to compare clinical features among adult COVID-19 patients in different age groups.Methods: Laboratory-confirmed adult COVID-19 infection cases between Dec 31, 2019 to March 8, 2020obtained from Neighboring Cities. Patients weredivided into five age groups:age＜30, 30-40, 40-50, 50-65, ≥65 y (elderly). Age, sex, history of chronic disease and epidemiology, symptoms, laboratory tests, and outcomes were compared among different agegroups. Binary logistic regression analysis was conducted to evaluate associated factors for severe or critical type.Results:We studied 299 cases. Median (IQR) age was 44(34,54) and 158 (53%) were male. Percent of bilateral involvement on chest radiographs was increased significantly with older age (p=0.005). 53.3% of 30-40 years, 50% of 40-50 years, 36.6% of ＜30 years and 36.2% of 50-60 years were imported case, none of the elderly were imported case. Among all the observed symptoms, only symptom of dyspnea was significantly different between the elderly group and other groups (p < 0.001).Proportion of severe or critical type was 2.4%, 5.3%, 9.5%, 14.5%, and 35%in patients with age＜30, 30-40, 40-50, 50-65, ≥65 (p < 0.001), respectively. At this point, ICU admissionrate, ARDSand shock rate and on medical treatment rate was increased especially in patients ≥65 years. 285 patients (95.3%) were curedand discharged, 12 patients (4.0%) were still on medical treatment in hospital. There were 2 (0.67%) deaths; these occurred among persons ≥65 y (p < 0.001). Old age, high HR on admission,high respiratory rate on admission, and history of chronic heart diseasewere independently associated with severe or critical .Conclusions:Proportion of severe or critical type increased with old age groups. Adults with old ageand high HR, R rate in admission and history of chronic heart disease were associated withsevere or criticaltype in COVID-19.

Comparative Clinical Characteristics Among Different Age Group of Adult COVID-19 Patients (preprint)

Introduction: Coronavirus disease (COVID-19) is a global infectious disease with a large burden of illness and high healthcare costs.Objectives: This study aimed to compare clinical features among adult COVID-19 patients in different age groups.Methods: Laboratory-confirmed adult COVID-19 infection cases between Dec 31, 2019 to March 8, 2020 obtained from Neighboring Cities. Patients were divided into five age groups: age༜30, 30–40, 40–50, 50–65, ≥ 65 y (elderly). Age, sex, history of chronic disease and epidemiology, symptoms, laboratory tests, and outcomes were compared among different age groups. Binary logistic regression analysis was conducted to evaluate associated factors for severe or critical type.Results: We studied 299 cases. Median (IQR) age was 44 (34,54) and 158 (53%) were male. Percent of bilateral involvement on chest radiographs was increased significantly with older age (p = 0.005). 53.3% of 30–40 years, 50% of 40–50 years, 36.6% of ༜30 years and 36.2% of 50–60 years were imported case, none of the elderly were imported case. Among all the observed symptoms, only symptom of dyspnea was significantly different between the elderly group and other groups (p < 0.001). Proportion of severe or critical type was 2.4%, 5.3%, 9.5%, 14.5%, and 35% in patients with age༜30, 30–40, 40–50, 50–65, ≥ 65 (p < 0.001), respectively. At this point, ICU admission rate, ARDS and shock rate and on medical treatment rate was increased especially in patients ≥ 65 years. 285 patients (95.3%) were cured and discharged, 12 patients (4.0%) were still on medical treatment in hospital. There were 2 (0.67%) deaths; these occurred among persons ≥ 65 y (p < 0.001). Old age, high HR on admission, high respiratory rate on admission, and history of chronic heart disease were independently associated with severe or critical .Conclusions: Proportion of severe or critical type increased with old age groups. Adults with old age and high HR, R rate in admission and history of chronic heart disease were associated with severe or critical type in COVID-19.

Symptoms at disease onset predict prognosis in COVID-19 disease (preprint)

Background: The main clinical manifestations of coronavirus disease 2019 (COVID-19) onset are respiratory symptoms, including cough, sputum and dyspnea. However, a significant proportion of patients initially manifested extra-respiratory symptoms, such as fever, myalgia and diarrhea. Here we compared the different characteristics and outcomes between the patients with respiratory symptoms and extra-respiratory symptoms at illness onset.Methods: The patients admitted to the respiratory departments from eight hospitals out of Wuhan with nucleic acid-positive of severe acute respiratory syndrome coronavirus (SARS-CoV-2) were recruited. Epidemiological information, clinical manifestations, laboratory findings, and radiological characteristics, treatment regimens and outcomes data were recorded and analyzed.Results: The median age of the recruited 541 subjects was 43 years (IQR, 33-55). Of the 541 subjects, 404 (74.5%) subjects had initial symptom that were respiratory, while 137 (25.5%) subjects had extra-respiratory symptoms. Respiratory COVID-19 subjects had more secondary bacterial infections (p<0.001), needed the intensive care unit more (p=0.005), non-invasive ventilation more (p=0.004), developed ARDS more (p=0.001) and needed longer to recover (p=0.003) compared to predominately extra-respiratory COVID-19 subjects. The multivariate model showed that age (OR = 1.04, p = 0.01) dyspnea (OR = 4.91, p < 0.001) and secondary bacterial infection (OR = 19.8, p < 0.001) were independently associated with development of ARDS among COVID-19 patients.Conclusion: we identify COVID-19 subjects with dyspnea at disease onset have worse prognosis. We also demonstrate age and secondary bacterial infections to be independently associated with ARDS development in subjects with COVID-19.

Early CT imaging markers of COVID-19 progression (preprint)

Background: Early recognition of patients who are prone to develop severe or critical COVID-19 pneumonia may improve its management and modify its outcome by better treatment regimens.Objective: To investigate Computed Tomography (CT)-based early markers of COVID-19 progression. Material and methods: Thirty-two COVID-19 patients were retrospectively enrolled, including 23 moderate cases who remained moderate until being cured and discharged from hospital, and 9 progressive cases who started with moderate pneumonia and later progressed to severe or critical pneumonia. Clinical and CT data in the early course of disease were reviewed and compared. The association between early features and progression of COVID-19 were analyzed. Results: The multivariate logistic regression analysis revealed that the progression of COVID-19 were significantly associated with older age and higher CT score of the right lower lobe in the early CT images. After adjustment for relevant covariates, the relationship between CT score of the right lower lobe and COVID-19 progression persisted (odds ratio 19.28, 95% confidence interval 1.07 - 348.34).Conclusions: Higher CT Score of the right lower lobe in early images and older age appeared to be promising biomarkers for early prediction of COVID-19 prognosis. Extensive involvement of the right lower lobe at the early stage may suggest a high risk of progression. 

Comparative clinical characteristics among different age group of adult COVID-19 Patients (preprint)

Introduction: Coronavirus disease (COVID-19) is a global infectious disease with a large burden of illness and high healthcare costs.Objectives: This study aimed to compare clinical features among adult COVID-19 patients in different age groups.Methods: Laboratory-confirmed adult COVID-19 infection cases between Dec 31, 2019 to March 8, 2020 obtained from Neighboring Cities. Patients were divided into five age groups: age＜30, 30-40, 40-50, 50-65, ≥65 y (elderly). Age, sex, history of chronic disease and epidemiology, symptoms, laboratory tests, and outcomes were compared among different age groups. Binary logistic regression analysis was conducted to evaluate associated factors for severe or critical type.Results: We studied 299 cases. Median (IQR) age was 44 (34,54) and 158 (53%) were male. Percent of bilateral involvement on chest radiographs was increased significantly with older age (p = 0.005). 53.3% of 30-40 years, 50% of 40-50 years, 36.6% of ＜30 years and 36.2% of 50-60 years were imported case, none of the elderly were imported case. Among all the observed symptoms, only symptom of dyspnea was significantly different between the elderly group and other groups (p < 0.001). Proportion of severe or critical type was 2.4%, 5.3%, 9.5%, 14.5%, and 35% in patients with age＜30, 30-40, 40-50, 50-65, ≥65 (p < 0.001), respectively.  At this point, ICU admission rate, ARDS and shock rate and on medical treatment rate was increased especially in patients ≥65 years. 285 patients (95.3%) were cured and discharged, 12 patients (4.0%) were still on medical treatment in hospital. There were 2 (0.67%) deaths; these occurred among persons ≥65 y (p < 0.001). Old age, high HR on admission, high respiratory rate on admission, and history of chronic heart disease were independently associated with severe or critical .Conclusions: Proportion of severe or critical type increased with old age groups. Adults with old age and high HR, R rate in admission and history of chronic heart disease were associated with severe or critical type in COVID-19.

Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China (preprint)

Background: Cases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Methods: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 12, 2020. Demographic, clinical, laboratory and radiological characteristics, medication therapy and outcomes were collected and analyzed. Patients were confirmed by PCR test. Results: Of the 104 patients, 48 (46.15%) were imported cases and 56 (53.85%) were indigenous cases; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 &ldquo:generations" was observed. Mean age was 43 (rang, 8-84) years (including 3 children) and 49 (47.12%) were male. Most patients had typical symptoms, 5 asymptomatic infections were found and 2 of them infected their relatives. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days. Just 9 of 16 severe patients required ICU care. Until Feb 12, 2020, 40 (38.46%) discharged and 1 (0.96%) died. For the antiviral treatment, 80 (76.92%) patients received traditional Chinese medicine therapy. Conclusions: Family but not community transmission occupied the main body of infections in the two centers. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. The incubation period of 8 patients exceeded 14 days.